Multilayer film for container, container including multilayer film, method for producing container, and drug solution-containing medical container

Abstract

To provide a multilayer film for containers, a container including the multilayer film, a method for producing a container including the multilayer film, and a drug solution-containing medical container in which a drug solution is housed in the container, in which the contents can be suppressed from being oxidized and altered by oxygen remaining in the container or the contents and / or penetrating and entering oxygen, adsorption of the contents to a film constituting the container can be suppressed, a decrease in the titer of a drug and adsorption of flavor can be suppressed, an increase in the adsorption amount of the contents to the film in a retort treatment step can be suppressed, uneven deformation of the film and occurrence of surface irregularities can be suppressed, and deformation of the container can be suppressed. A multilayer film for containers, including: an outer film which is a transparent oxygen barrier film; an intermediate film which is a coextruded film having an oxygen absorbing layer; and an inner film which is a coextruded film having a cyclic polyolefin layer containing cyclic polyolefin, in which the intermediate film has a symmetrical laminated structure having a skin layer with the oxygen absorbing layer as a core layer, and the inner film has a symmetrical laminated structure having a skin layer with the cyclic polyolefin layer as a core layer.

Description

MULTILAYER FILM FOR CONTAINER, CONTAINER INCLUDING MULTILAYER FILM, METHOD FOR PRODUCING CONTAINER, AND DRUG SOLUTION-CONTAINING MEDICAL CONTAINER

[0001] The present invention relates to a multilayer film for containers, a container including the multilayer film for containers, a method for producing a container, and a drug solution-containing medical container.

[0002] In a container such as a bag made of a film, the contents may be oxidized and altered by oxygen remaining in the container and the contents and / or oxygen entering by penetrating a container wall. In addition, in a container such as a bag made of a film, adsorption of the contents to a film constituting the container may be a problem. Adsorption of the contents to the film may cause a problem of lowering the titer of a drug in the medical field and may cause a problem of adsorption of flavor in the food field. In order to solve these problems, for example, Patent Literature 1 discloses a multilayer barrier film in which an inner layer made of a heat-sealable resin, an aroma retaining layer made of a cyclic olefin copolymer resin, an oxygen absorption barrier layer containing an oxidizing polymer and a transition metal catalyst, and an outer layer made of a biaxially oriented film are sequentially laminated in this order from the inside of a container. However, in a conventional container formed of a multilayer film, there has been a possibility that an adsorption amount of the contents to a film may increase in a step of high-pressure steam sterilization by retort treatment using an autoclave adopted in a retort food or a drug solution bag. Furthermore, due to the difference in heat resistance and shrinkage rate among the layers, there has been a possibility that the multilayer film may be unevenly deformed, or irregularities may be formed on the surface of the multilayer film, and furthermore, there has been a possibility that the container itself may be deformed.

[0003] Patent Literature 1: JP-A-2004-243523Problems to be Solved by Invention

[0004] An object of the present invention is to provide a multilayer film for containers, a container including the multilayer film, a method for producing a container using the multilayer film, and a drug solution-containing medical container in which a drug solution is housed in the container, in which the contents can be suppressed from being oxidized and altered by oxygen remaining in the container or the contents and / or penetrating and entering oxygen, adsorption of the contents to a film constituting the container can be suppressed, a decrease in the titer of a drug and adsorption of flavor can be suppressed, an increase in the adsorption amount of the contents to the film in a retort treatment step can be suppressed, uneven deformation of the film and occurrence of surface irregularities can be suppressed, and deformation of the container can be suppressed.Solution to Problems

[0005] The present inventor has conducted intensive studies in order to solve the above problems. Then, the present inventor has found that the above problems can be solved by a multilayer film for containers having a specific configuration, a container including the multilayer film, a method for producing a container using the multilayer film, and a drug solution-containing medical container in which a drug solution is housed in the container, and has completed the present invention. Specifically, the present invention is as follows. (Item 1) A multilayer film for containers, including: an outer film which is a transparent oxygen barrier film; an intermediate film which is a coextruded film having an oxygen absorbing layer; and an inner film which is a coextruded film having a cyclic polyolefin layer containing cyclic polyolefin, in which the intermediate film has a symmetrical laminated structure having a skin layer with the oxygen absorbing layer as a core layer, and the inner film has a symmetrical laminated structure having a skin layer with the cyclic polyolefin layer as a core layer. (Item 2) The multilayer film for containers according to item 1, in which the intermediate film has a skin layer containing polyolefin on both surfaces of the core layer via an adhesive layer containing a polyethylene-based adhesive resin. (Item 3] The multilayer film for containers according to item 2, in which the skin layer containing polyolefin contains 50 mass% or more of linear low density polyethylene and equal or more than 30 mass% and less than 50 mass% of high density polyethylene. (Item 4) The multilayer film for containers according to any one of items 1 to 3, in which the inner film is flat tubular, and has the intermediate film and the outer film on both surfaces of the inner film. (Item 5) A container including the multilayer film for containers according to any one of items 1 to 4. (Item 6) A method for producing a container, including sealing the inner film of the multilayer film for containers according to any one of items 1 to 4. (Item 7) A drug solution-containing medical container, in which a drug solution is housed in the container according to item 5.Effects of Invention

[0006] According to the present invention, there is provided a multilayer film for containers, a container including the multilayer film, a method for producing a container including the multilayer film, and a drug solution-containing medical container in which a drug solution is housed in the container, in which the contents can be suppressed from being oxidized and altered by oxygen remaining in the container or the contents and / or penetrating and entering oxygen, adsorption of the contents to a film constituting the container can be suppressed, a decrease in the titer of a drug and adsorption of flavor can be suppressed, an increase in the adsorption amount of the contents to the film in a retort treatment step can be suppressed, uneven deformation of the film and occurrence of surface irregularities can be suppressed, and deformation of the container can be suppressed. In this multilayer film for containers, deformation of the multilayer film for containers is suppressed, and when the multilayer film for containers is formed into a medical container, deterioration due to oxidation of a drug can be suppressed, and adsorption of the drug to the film can be suppressed, so that a decrease in the titer of the drug can be suppressed, container appearance is excellent, and the period during which the drug can be effectively stored can be set to a long period.

[0007] Fig. 1 is a schematic view of a multilayer film for containers according to an embodiment of the present invention. Fig. 2 is a schematic view of another multilayer film for containers according to an embodiment of the present invention. Fig. 3 is a container according to an embodiment of the present invention.

[0008] Hereinafter, a multilayer film for containers, a container including the multilayer film for containers, a method for producing a container using the multilayer film for containers, and a drug solution-containing medical container in which a drug solution is housed in the container, according to the present invention, will be described in detail.

[0009] (Multilayer film for containers) Fig. 1 is a schematic view of a multilayer film for containers according to an embodiment of the present invention. A multilayer film F for containers illustrated in Fig. 1 includes an outer film 1 which is a transparent oxygen barrier film, an intermediate film 2 which is a coextruded film having an oxygen absorbing layer, and an inner film 3 which is a coextruded film having a cyclic polyolefin layer containing cyclic polyolefin, in which the outer film 1 and the intermediate film 2 are bonded to each other by an adhesive layer 4 (dry lamination adhesive layer), and the intermediate film 2 and the inner film 3 are bonded to each other by an adhesive layer 5 (dry lamination adhesive layer).

[0010] In the multilayer film F for containers illustrated in Fig. 1, the outer film 1 is a layer that mainly has a function as a substrate film, has highest heat resistance, and has a high oxygen barrier function. The intermediate film 2 is a layer mainly having oxygen absorbing capability. The inner film 3 is a layer having a function of mainly preventing adsorption of the contents to the multilayer film for containers. In the multilayer film F for containers illustrated in Fig. 1, the intermediate film 2 has a symmetrical laminated structure having an intermediate film skin layer 21 with, as a core layer, an intermediate film core layer 23 which an oxygen absorbing layer. In the multilayer film F for containers illustrated in Fig. 1, the inner film 3 has a symmetrical laminated structure having an inner film skin layer 31 with, as a core layer, an inner film core layer 33 which is a cyclic polyolefin film layer.

[0011] Fig. 2 is a schematic view of a tubular multilayer film TF for containers according to an embodiment of the present invention. The multilayer film TF for containers illustrated in Fig. 2 is a coextruded film having an outer film 1 which is a transparent oxygen barrier film, an intermediate film 2 which is a coextruded film having an oxygen absorbing layer, and a tubular inner film 3a which is a coextruded film having a cyclic polyolefin layer containing cyclic polyolefin. In the multilayer film TF for containers illustrated in Fig. 2, the outer film 1 and the intermediate film 2 are similar to the outer film 1 and the intermediate film 2 in the multilayer film F for containers illustrated in Fig. 1. In the multilayer film TF for containers illustrated in Fig. 2, the inner film 3a is a tubular film having a symmetrical laminated structure having an inner film skin layer 31 with, as a core layer, an inner film core layer 33 which is a cyclic polyolefin film layer. In Fig. 2, the inner film 3a illustrates a state in which a tubular film is folded and flattened.

[0012] <Outer film> The outer film is a transparent oxygen barrier film. The oxygen transmittance of the outer film is, for example, 10 mL / (m2・day・MPa) or less, preferably 5 mL / (m2・day・MPa) or less, and more preferably 3 mL / (m2・day・MPa) or less. With such an oxygen transmittance, oxygen entering from the outer film can be sufficiently blocked, and the oxygen absorbing layer of the intermediate film can function to exclusively absorb oxygen dissolved in the contents on the inner film side. As a result, the amount of the oxygen absorbing resin in the oxygen absorbing layer can be minimized, and the thickness of the oxygen absorbing layer can be reduced.

[0013] The water vapor transmittance of the outer film is not particularly limited. For example, the water vapor transmission rate can be 1.0 g / (m2・day) or less, preferably 0.5 g / (m2・day) or less, and more preferably 0.3 g / (m2・day) or less. When the water vapor transmittance is high, there is a possibility that the intermediate film may be whitened by absorbing moisture during high-pressure steam sterilization, leading to deterioration of transparency. In particular, when the intermediate film has a vinyl alcohol-based polymer layer such as an ethylene-vinyl alcohol copolymer, lowering the water vapor transmittance of the outer film is effective from the viewpoint of preventing whitening.

[0014] The outer film is a film in which an oxygen barrier layer, preferably an oxygen and water vapor barrier layer, is provided on a transparent substrate film. More specifically, an example thereof is a film in which a vapor deposited layer of an inorganic compound is provided on a substrate film which is a biaxially oriented film using polyester such as polyethylene terephthalate, polyolefin such as polypropylene, and polyamide. Examples of the inorganic compound constituting the vapor deposited layer include one or more selected from the group consisting of inorganic oxides such as silicon oxide and / or aluminum oxide, inorganic nitrides such as silicon nitride, and inorganic carbides. The film is preferably a film including: a vapor deposited film layer on at least one surface of a substrate film; and an oxygen barrier topcoat layer for protecting the vapor deposition film layer on a surface of the vapor deposited film layer which is not in contact with the substrate film. Among these outer films, an outer film in which silicon oxide is vapor-deposited on a biaxially oriented film of polyethylene terephthalate is preferable, because it has excellent gas barrier properties and also has tensile strength, dimensional stability, and heat resistance.

[0015] Examples of a commercially available product of such a transparent oxygen barrier film include, as a transparent silica-deposited high gas barrier film, a trade name ”TECHBARRIER” manufactured by Mitsubishi Chemical Corporation and a trade name ”GL FILM” manufactured by Toppan Printing Co., Ltd.

[0016] (Configuration of outer film) The outer film is transparent, and it is preferable that, for example, the total light transmissivity is 70% or more, and the haze (cloudiness) is 10% or less. The outer film may be colored and transparent. The thickness of the outer film is not particularly limited. For example, the thickness is 3 μm or more, preferably 5 μm or more, and more preferably 8 μm or more, and can be, for example, 50 μm or less, preferably 30 μm or less, and more preferably 20 μm or less. In the outer film, a printing layer for displaying information may be provided on at least a part of the surface on the intermediate film side. In the outer film, an easily writing layer (ink receiving layer) on which information can be described may be provided on at least a part of the surface opposite the intermediate film.

[0017] <Intermediate film> The intermediate film is a co-extruded film having a symmetrical structure in which a core layer as an oxygen absorbing layer is a central layer, and a skin layer is provided on both sides of the core layer. Since the laminated film has a symmetrical structure, curling of the film can be suppressed. The intermediate film has a skin layer containing polyolefin as an outer layer on both surfaces of the core layer via an adhesive layer of the intermediate film.

[0018] (Oxygen absorbing layer (intermediate film core layer)) The oxygen absorbing layer as the core layer of the intermediate film is a layer including an oxygen absorbing resin composition. A usable example of the oxygen absorbing resin composition is a resin composition that contains as a main component an ethylene-vinyl alcohol copolymer having an ethylene content of less than 50 mol% and that contains 0.1% or less of a transition metal salt and a polyene-based polymer which is a polymer of a conjugated diene compound having an unsaturated double bond. This resin composition absorbs oxygen while generating alcohol, aldehyde, ketone, and carboxylic acid by an oxidative cleavage reaction of a polyene-based polymer with a transition metal salt as a catalyst in the presence of oxygen. The oxygen absorbing resin composition in the present invention preferably has an ability to absorb 30cc or more of oxygen per 1 g. Examples of a commercially available product of such an oxygen absorbing resin composition include ”EVAL” AP series manufactured by Kuraray Co., Ltd.

[0019] The thickness of the oxygen absorbing layer is not particularly limited, but is, for example, 5 μm or more, and preferably 8 μm or more, and is, for example, 50 μm or less, and preferably 30 μm or less. When the thickness of the oxygen absorbing layer is less than 5 μm, the oxygen absorbing capability may be insufficient, and film breakage may occur during film formation of the coextruded film, in which the oxygen absorbing layer is partially interrupted, causing formation of a portion where the oxygen absorbing layer does not exist. When the thickness of the oxygen absorbing layer exceeds 50 μm, moldability may be deteriorated when the intermediate film is coextruded.

[0020] (Intermediate film skin layer) The skin layer of the intermediate film is not particularly limited as long as it is a layer having a function of film formation stability at the time of film formation and a water vapor barrier function of preventing moisture reaching the oxygen absorbing layer of which the barrier properties are deteriorated by moisture. The skin layer of the intermediate film is preferably a polyolefin layer containing polyolefin. Examples of the polyolefin contained in the polyolefin layer include one or more of polypropylene (hereinafter, may be referred to as ”PP”) and polyethylene (hereinafter, may be referred to as ”PE”).

[0021] When PP is used as the polyolefin, for example, a flexible PP composition containing an elastomer is preferably used. When PE is used as the polyolefin, a PE composition containing linear low density polyethylene (hereinafter, may be referred to as ”LLDPE”) is preferably used from the viewpoint of excellent transparency and film strength. The LLDPE is preferably produced using a single site catalyst. The density range of the LLDPE is, for example, 0.860 g / cm3or more, and preferably 0.900 g / cm3or more, and is, for example, 0.940 g / cm3or less, and preferably 0.917 g / cm3or less. Examples of the LLDPE produced using the single site catalyst include, as commercially available products, a trade name ”Harmolex” manufactured by Japan Polyethylene Corporation, a trade name ”Umerit” (registered trademark) manufactured by Ube Industries, Ltd., and a trade name ”Evolue” (registered trademark) manufactured by Prime Polymer Co., Ltd.

[0022] The melt mass flow rate (hereinafter, may be referred to as ”MFR”) of polyolefin is not particularly limited, and only has to be appropriately selected in consideration of extrusion moldability and the like when the intermediate film is produced by co-extrusion. For example, the MFR can be set to more than or equal to 0.5 g / 10 min and less than and equal to 10 g / 10 min. Here, MFR is a value measured in accordance with JIS K7210-1:2014 under a load of 2.16 kg, at a temperature of 190°C for PE and 230°C for PP.

[0023] When a PE composition containing LLDPE is used as the polyolefin constituting the skin layer of the intermediate film, it is preferable to use a PE composition containing 50 mass% or more of LLDPE. A preferable usable example of the resin other than LLDPE contained in an amount of less than 50 mass% in the PE composition is high density polyethylene (hereinafter, may be referred to as ”HDPE”) from the viewpoint of heat resistance and suppression of blocking between intermediate films. By using a composition layer of LLDPE and HDPE as the skin layer of the intermediate film and adjusting the mixing ratio thereof, it is possible to obtain an intermediate film of a multilayer film for containers which has heat resistance adapted to high-pressure steam sterilization conditions adopted according to the thermal stability of the contents. If the heat resistance of the skin layer of the intermediate film is insufficient, the layers of the intermediate film may be peeled off during high-pressure steam sterilization, or the container including the bag-shaped multilayer film for containers may be broken. When the contents are unstable at 121°C under the high-pressure steam sterilization conditions, for example, the mixing ratio of HDPE is preferably in a range of equal to or more than 10 mass% and less than 30 mass% with respect to 100 mass% of the entire skin layer because of excellent transparency, and more preferably in a range of equal to or more than 30 mass% or more and less than 50 mass% because it is possible to achieve both sufficient transparency and excellent heat resistance and sterilize a container including the multilayer film for containers with high-pressure steam at a high temperature, for example, 121°C.

[0024] The density of HDPE used in the mixture with LLDPE is, for example, 0.940 g / cm3or more, preferably 0.945 g / cm3or more, and is, for example, 0.970 g / cm3or less. The density of HDPE is preferably 0.945 g / cm3or more and 0.970 g / cm3or less because a skin layer excellent in heat resistance can be formed. The MFR of HDPE is, for example, equal to or more than 0.1 g / 10 min, and preferably equal to or more than 3 g / 10 min, and is, for example, less than and equal to 30 g / 10 min, and preferably less than and equal to 25 g / 10 min. From the viewpoint of film moldability, the MFR of HDPE is preferably equal to or more than 3 g / 10 min and less than and equal to 25 g / 10 min.

[0025] The thickness of the skin layer of the intermediate film is, for example, 5 μm or more, and preferably 10 μm or more, and is, for example, 100 μm or less, and preferably 80 μm or less. When the thickness of the skin layer of the intermediate film is less than 5 μm, film breakage may occur during film formation of the coextruded film, and the thickness is more preferably 10 μm or more in consideration of water vapor barrier properties. When the thickness of the skin layer of the intermediate film exceeds 100 μm, the thickness of the intermediate film exceeds 200 μm, and there is a possibility that processability of dry lamination or the like when a multilayer film for containers is produced using the intermediate film may be deteriorated, and the thickness is more preferably 80 μm or less in consideration of processability.

[0026] (Intermediate film adhesive layer) The adhesive layer of the intermediate film is not particularly limited as long as it contains an adhesive resin and can bond the core layer and the skin layer of the intermediate film during co-extrusion molding. Examples of the adhesive resin include an adhesive olefin-based thermoplastic elastomer and modified polyolefin obtained by adding unsaturated dicarboxylic anhydride such as maleic anhydride and / or a monomer having a functional group such as unsaturated carboxylic acid to polyolefin such as PE or PP to introduce a functional group. Among them, modified polyolefin is preferable. Of the modified polyolefin, a PE-based adhesive resin including modified PE in which a polar group is introduced by adding maleic anhydride or the like is preferable, because interlayer adhesive strength is increased. Especially, it is more preferable that the polyolefin layer adjacent to the adhesive layer is a PE composition layer containing LLDPE, and the adhesive layer is a PE-based adhesive resin, because the interlayer adhesive strength does not decrease after high-pressure steam sterilization. Examples of a commercially available product of the adhesive resin include trade names ”ZELAS” and ”MODIC” manufactured by Mitsubishi Chemical Corporation and a trade name ”ADMER” manufactured by Mitsui Chemicals, Inc.

[0027] By increasing the interlayer adhesive strength between the oxygen absorbing layer which is the core layer of the intermediate film and the adhesive layer of the intermediate film, it is possible to suppress deformation when a container including the multilayer film for containers is sterilized with high-pressure steam. Furthermore, it is possible to suppress the occurrence of a problem that hot water at a high temperature enters from the end surface of the intermediate film portion into the boundary surface between the adhesive layer and the oxygen absorbing layer of the intermediate film at the time of high-pressure steam sterilization, and the oxygen absorbing layer absorbs moisture to deteriorate oxygen absorbability and barrier properties, or the boundary surface between the adhesive layer and the oxygen absorbing layer of the intermediate film is partially peeled off to cause appearance defects. This makes it possible to maintain high oxygen absorbability and barrier properties of the oxygen absorbing layer. The interlayer strength between the adhesive layer and the oxygen absorbing layer of the intermediate film is, for example, preferably equal to or more than 8 N / 25 mm in width before high-pressure steam sterilization, preferably not reduced even after high-pressure steam sterilization, and more preferably improved after high-pressure steam sterilization.

[0028] The thickness of the adhesive layer of the intermediate film is, for example, preferably 5 μm or more and 20 μm or less. When the thickness is less than 5 μm, there is a possibility that film breakage may occur when the intermediate film is formed as a coextruded film, which may cause variation or reduction in interlayer adhesive strength. When the thickness is more than 20 μm, wrinkles may be generated in the intermediate film and the multilayer film for containers due to the soft adhesive layer.

[0029] (Method for producing intermediate film) The method for producing the intermediate film is not particularly limited, and a known method for producing a film can be used. Examples thereof include a T-die casting method and a water-cooled or air-cooled inflation molding method. The inflation molding method is also referred to as blown film extrusion. Among them, a T-die casting method and a water-cooled inflation molding method are preferable because a film excellent in transparency can be obtained, and an air-cooled inflation molding method is preferable because a film having a wide width and an appropriate thickness can be molded at a relatively low cost.

[0030] (Configuration of intermediate film) The thickness ratio of the layers in the intermediate film can be, for example, 10:20 to 100:2 to 10 for core layer: skin layer: adhesive layer. When the thickness of the skin layer is increased, moisture transmission into the oxygen absorbing layer as a core layer can be further suppressed. When the thickness of the oxygen absorbing layer as a core layer exceeds 50 μm, moldability may be deteriorated when the intermediate film is subjected to coextrusion molding, particularly coextrusion inflation molding. Therefore, the thickness of the oxygen absorbing layer is preferably 50 μm or less. In the case of coextrusion inflation molding of an intermediate film including the oxygen absorbing layer having a thickness of more than 50 μm, in which the melting point of the ethylene-vinyl alcohol copolymer as the main component of the oxygen absorbing layer as the core layer is the highest, the molding temperature needs to be set high in order to increase the discharge volume for thickening the core layer, and bubble stability in inflation molding of the intermediate film may be deteriorated.

[0031] <Inner film> The inner film in the present invention is the thickest main film in the multilayer film for containers of the present invention. The inner film is a coextruded film having a cyclic polyolefin layer containing cyclic polyolefin (hereinafter, may be referred to as ”COP”) as a core layer serving as a central layer of a symmetrical structure. Since the inner film has a laminated structure symmetrical about the core layer, curling of the multilayer film for containers can be suppressed. The inner film has a skin layer as an outer layer on both sides of the core layer via an intermediate layer of the inner film.

[0032] Since the inner film has the core layer containing COP, it is possible to prevent the components of the contents from being adsorbed to a container when the container is formed with the multilayer film for containers. In addition, it is possible to prevent a reaction product generated when the oxygen absorbing layer of the intermediate film absorbs oxygen from diffusing from the container to the inside of the container. Furthermore, when the printing layer is formed on the multilayer film for containers, the inner film has a function of preventing the leaching of a component derived from the printing ink used for the printing layer, in addition to the barrier properties of the oxygen absorbing layer.

[0033] (COP layer (inner film core layer)) Since COP rarely adsorbs or absorbs a drug, it is possible to suppress a decrease in the medicinal ingredient of the drug solution to be housed. In addition, COP is low in water vapor transmissivity and has water vapor barrier properties, and rarely eludes impurities and is excellent in hygiene properties. Furthermore, COP is excellent in heat resistance and transparency, and thus is suitable for use in a medical container that needs to be sterilized with high-pressure steam and that requires the contents to be visible from the outside.

[0034] Examples of the COP include one or more selected from the group consisting of a ring-opening polymer of a cyclic olefin monomer, a hydrogenated product of the ring-opening polymer, an addition polymer of a cyclic olefin monomer, an addition copolymer with another monomer copolymerizable with a cyclic olefin monomer, and the like. Among them, a hydrogenated product of a ring-opening polymer of a cyclic olefin monomer is preferable from the viewpoint of heat resistance, mechanical strength, and the like.

[0035] The cyclic olefin monomer is not particularly limited, and examples thereof include a norbornene-based monomer and a monocyclic cyclic olefin monomer. Examples of the norbornene-based monomer include norbornene, dicyclopentadiene, methanotetrahydrofluorene, and tetracyclododecene. Examples of the monocyclic cyclic olefin monomer include cyclohexene, cycloheptene, and cyclooctene. One kind or two or more kinds of cyclic olefin monomers can be used.

[0036] The glass transition temperature (hereinafter, may be referred to as ”Tg”) of the COP is not particularly limited. The Tg is, for example, 70°C or higher, and preferably 100°C or higher, and is, for example, 180°C or lower, and preferably 140°C or lower. The Tg can be measured by a differential scanning calorimeter in accordance with JIS K 7121. The Tg may also be a value described in a catalog, a technical document, or the like. When the Tg is lower than 70°C, there is a case where the film is not suitable for high-pressure steam sterilization. On the other hand, when the Tg exceeds 180°C, the moldability of the inner film may be deteriorated.

[0037] In the present invention, it is preferable to use, as the COP, a mixture of a plurality of COPs having good compatibility and different Tg’s at an appropriate ratio in order to achieve both heat resistance to withstand the intended high-pressure steam sterilization temperature and moldability. For example, in the case of a multilayer film for containers to be subjected to high-pressure steam sterilization at 121°C, the Tg of the COP is preferably about 118°C or higher. Note that only one Tg is observed in the COP mixture in which COPs having good compatibility are mixed.

[0038] Examples of a commercially available product of COP include, as the addition (co) polymer of a cyclic olefin monomer, a trade name ”APEL” (registered trademark) manufactured by Mitsui Chemicals, Inc. and a trade name ”TOPAS” (registered trademark) manufactured by TICONA, and as the hydrogenated product of a ring-opening polymer of a cyclic olefin monomer, trade names ”ZEONOR” (registered trademark) and ”ZEONEX” (registered trademark) manufactured by Zeon Corporation.

[0039] The thickness of the COP layer is not particularly limited, but is, for example, 5 μm or more, and preferably 10 μm or more, and is, for example, 100 μm or less, and preferably 50 μm or less. When the thickness is less than 5 μm, film breakage may occur during film formation of the coextruded film, and the barrier properties may be insufficient. If the thickness exceeds 100 μm, the COP layer becomes hard, moldability is deteriorated, and there is a risk that the flexibility of the inner film and thus of the multilayer film for containers may be impaired.

[0040] (Inner film skin layer) The skin layer of the inner film preferably contains HDPE. The skin layer of the inner film is the innermost surface layer in contact with the contents in a container including the multilayer film for containers. The skin layer of the inner film also functions as a sealant layer and is heat-sealed to constitute a peripheral edge portion of the container. When the skin layer of the inner film is a layer containing HDPE, it is possible to suppress blocking between the inner surfaces of the container at the time of producing the inner film or after high-pressure steam sterilization of the container containing the contents, suppress peeling of the heat-sealed part, and constitute a container excellent in heat resistance.

[0041] The density of HDPE used for the skin layer of the inner film is, for example, 0.940 g / cm3or more, preferably 0.945 g / cm3or more, and more preferably 0.960 g / cm3or more, and is, for example, 0.970 g / cm3or less. From the viewpoint of heat resistance, it is preferably 0.945 g / cm3or more. The MFR of HDPE used for the skin layer of the inner film is, for example, equal to or more than 0.1 g / 10 min, and preferably equal to or more than 1.0 g / 10 min, and is, for example, less than and equal to 30 g / 10 min, and preferably less than and equal to 25 g / 10 min. From the viewpoint of film moldability, the MFR of HDPE is preferably equal to or more than 1.0 g / 10 min and less than and equal to 25 g / 10 min. The suitable content of HDPE in the skin layer of the inner film varies depending on the density of HDPE, and is not particularly limited. For example, in the case of HDPE having a density of 0.945 g / cm3or more and 0.970 g / cm3or less, it is possible to form a container having sufficient heat resistance with less characteristics deterioration even by high-pressure steam sterilization at 121°C, when the content of HDPE in the skin layer of the inner film is 40 mass% or more. In order to develop more stable heat resistance and blocking resistance, the content of HDPE in the skin layer of the inner film is preferably 60 mass% or more, more preferably 70 mass% or more, and further preferably 100 mass%.

[0042] When a container is produced with the multilayer film for containers, the skin layer of the inner film is heat-sealed to constitute the inner surface of the container and the peripheral portion thereof. Among them, the peripheral portion is required to have heat resistance enough not to be peeled off even in high-pressure steam sterilization, and thus the HDPE used in the skin layer of the inner film is required to have heat resistance superior to that of the HDPE used by being mixed with LLDPE in the skin layer of the intermediate film. Therefore, it is preferable that the HDPE used in the skin layer of the inner film has a higher density and a lower MFR than the HDPE used by being mixed with LLDPE in the skin layer of the intermediate film. Specifically, the density of the HDPE used in the skin layer of the inner film is 0.955 g / cm3or more, and preferably 0.960 g / cm3or more, and the MFR of the HDPE used in the skin layer of the inner film is 3.0 g / 10 min or less, and preferably 2.5 g / 10 min or less. More specifically, the skin layer of the inner film is preferably constituted by HDPE alone or a mixture of HDPE and LLDPE, and the mass ratio of LLDPE:HDPE is preferably 40 to 0:60 to 100. When the skin layer of the intermediate film adjacent to the skin layer of the inner film contains HDPE in an amount of equal to or more than 30 mass% and less than 50 mass%, the content of HDPE in the skin layer of the intermediate film is preferably lower than the content of HDPE in the skin layer of the inner film.

[0043] Since the skin layer of the intermediate film is the thickest and the main layer in the intermediate film, and is relatively thick (5 μm or more and 100 μm or less, and preferably 10 μm or more and 80 μm or less), it is sufficient that the skin layer has heat resistance to such an extent that the skin layer is not vigorously shrunk by high-pressure steam sterilization, and thus it is preferable that the content of HDPE is small from the viewpoint of transparency and flexibility of the container. On the other hand, since the skin layer of the inner film also functions as a heat-sealing layer of the multilayer film for containers, and is required to have heat resistance so as not to be peeled off even when the container is sterilized with high-pressure steam, it is preferable that the content of HDPE is large.

[0044] The skin layer of the intermediate film may contain a plurality of HDPEs having different densities. Furthermore, for the purpose of enhancing molding stability, it is also preferable to mix a polyethylene resin such as a high pressure low density polyethylene having a density of 0.910 g / cm3or more and 0.935 g / cm3or less.

[0045] The thickness of the skin layer of the inner film is, for example, preferably 5 μm or more and 50 μm or less.

[0046] (Inner film intermediate layer) The intermediate layer of the inner film is a layer positioned between the cyclic polyolefin layer as the core layer of the inner film and the skin layer, and includes polyolefin such as PE or PP. It is preferable to contain PE, because the interlayer adhesive strength with the adjacent skin layer increases. Further, it is preferable to contain LLDPE among PEs, because the interlayer adhesive strength with the cyclic polyolefin layer as the adjacent core layer increases, and transparency, flexibility, and impact resistance are excellent. Furthermore, a composition of LLDPE and HDPE is more preferable, because excellent heat resistance is obtained. The mass ratio of LLDPE:HDPE is preferably 60 to 95:40 to 5 and more preferably 70 to 90:30 to 10.

[0047] The LLDPE used for the intermediate layer of the inner film is the same as the LLDPE used for the polyolefin layer of the intermediate film. With such LLDPE, it is possible to suppress the occurrence of appearance defects caused by wrinkles, air bubbles, and the like after high-pressure steam sterilization of a container including the multilayer film for containers. In particular, LLDPE having a density in a range of 0.900 g / cm3or more and 0.917 g / cm3or less has excellent heat resistance and excellent adhesiveness with the cyclic polyolefin layer even after high-pressure steam sterilization. The intermediate layer of the inner film is the thickest and main layer in the inner film. The intermediate layer of the inner film is also preferably the thickest layer in the multilayer film for containers. A specific thickness of the intermediate layer is not particularly limited, but is, for example, 40 μm or more, and is, for example, 120 μm or less, and preferably 80 μm or less.

[0048] (Method for producing inner film) The method for producing the inner film is not particularly limited, and a known method for producing a film can be used. Examples thereof include the same methods as the methods of producing the intermediate film. Among them, an inflation molding method is preferable, and a water-cooled inflation molding method by which a film excellent in transparency is obtained is particularly preferable. In the inflation molding method, a tubular film can be produced by blowing sterile air, so that the inner surface of the tube serving as the inner surface of the container is not exposed to outside air, and excellent hygiene properties are obtained, which is preferable. Further, in order to enhance hygiene properties, it is more preferable to seal the start end and the terminal end of the tube by heat sealing so that the inner surface of the tube does not come into contact with outside air.

[0049] (Configuration of inner film) The thickness ratio of the layers in the inner film is, for example, preferably 10:20 to 100:2 to 10 for COP layer (core layer):intermediate layer: skin layer (sealant layer).

[0050] <Configuration of multilayer film for containers> The multilayer film for containers of the present invention is a film in which an outer film, an intermediate film, and an inner film are laminated in this order. Although the films can be laminated by an adhesive, an adhesive resin, and heat lamination, it is preferable to bond the films by a dry lamination layer using an adhesive for dry lamination, because strong adhesion is possible. As the adhesive for dry lamination, two-liquid polyurethane-based adhesives for reacting an ether-based or ester-based polyol with an aliphatic or aromatic isocyanate can be used. Among them, it is preferable to use a two-component polyurethane-based adhesive for reacting an ester-based polyol with an aliphatic isocyanate. With the two-component polyurethane-based adhesive for reacting an ester-based polyol with an aliphatic isocyanate, it is possible to form a dry lamination adhesive layer which is excellent in heat resistance and in which the lamination strength is not reduced even by high-pressure steam sterilization, and it is possible, unlike an aromatic isocyanate, to form a dry lamination adhesive layer without generating aromatic amine suspected of being carcinogenic by hydrolysis with hot water.

[0051] In the multilayer film for containers of the present invention, both the intermediate film having oxygen absorbing capability and the inner film having a low adsorption function and barrier properties against chemical substances are obtained by coextrusion molding, and each of the intermediate film and the inner film has a sufficient thickness and all required functions. By bonding and laminating these films and an outer film having an oxygen barrier function by a dry lamination method, shrinkage caused by poor heat resistance, delamination caused by shrinkage, wrinkles of the film, and the like can be suppressed.

[0052] As illustrated in Fig. 2, the multilayer film for containers of the present invention preferably has a structure in which the inner film is flat tubular, and the intermediate film and the outer film are laminated on both surfaces of the inner film by an adhesive for dry lamination. Thus, a container can be produced without exposing, to outside air, the skin layer (sealant layer) of the inner film as the tube inner surface of the inner film to come into contact with the contents, and the container can be made excellent in hygiene properties without being contaminated with bacteria and foreign matters. In addition, since the inner film is tubular, the inner surfaces of the inner film are not rubbed against each other and are not shifted.

[0053] <Method for producing multilayer film for container> The method for producing the multilayer film for containers is not particularly limited. An example thereof is a method for stacking an outer film, an intermediate film, and an inner film in this order, and laminating and integrating the films by a measure such as an adhesive, an adhesive resin, or heat lamination. Since the films can be strongly bonded, a method for laminating and integrating the films using an adhesive for dry lamination is preferable.

[0054] An example of the method for producing the multilayer film for containers illustrated in Fig. 2 is the following method. As the inner film, a film wound in a flat tube state is prepared. As the intermediate film, one obtained by cutting open a tubular film to form one film, one obtained by cutting off both side ends of a flat tube into two pieces and winding the pieces, or a film produced by a T-die casting method is prepared. Next, the intermediate film and the outer film are laminated in this order on one outer surface of the inner film of the flat tube by a dry lamination method, and the intermediate film and the outer film are laminated in this order on the other outer surface of the inner film of the flat tube by a dry lamination method. As a result, it is possible to obtain a multilayer film for containers in which an intermediate film and an outer film are bonded to both surfaces of a tubular inner film. More specifically, a preferable production method is firstly laminating a wide outer film and a wide intermediate film by dry lamination, slitting the obtained film to form a narrow laminated film, and laminating the narrow laminated film on both surfaces, one by one, of an inner film of a flat tube by a dry lamination method. Here, the wide outer film and the wide intermediate film specifically mean an outer film and an intermediate film each having a width that is more than 1 time and preferably more than 2 times the width of the flat tube. The narrow laminated film means a laminated film having a width similar to the width of the flat tube. The laminated film having a width that is 2 times or more the width of the flat tube can be slit to produce a plurality of narrow laminated films at the same time, and therefore high productivity can be obtained. According to this production method, the number of times of lamination can be reduced as compared with the case where an intermediate film and an outer film are sequentially laminated one by one on both surfaces of a tubular inner film, and productivity is high. Furthermore, since the adhesive used in the dry lamination method can be applied on an outer film having the highest heat resistance for lamination, productivity is high, and the risk of occurrence of defects such as wrinkles and meandering can be reduced. In other methods, the number of times of lamination may increase, and the risk of occurrence of defects such as wrinkles and meandering may increase by applying and drying an adhesive on an intermediate film or an inner film inferior in heat resistance to an outer film. Further, while the laminated film of the outer film and the intermediate film has a thickness of about 50 μm to about 120 μm, the inner film has a thickness of about 100 μm to about 200 μm, and the inner film having a flat tube shape has a thickness of about 200 μm to about 400 μm. Since the thickness of the laminated film of the outer film and the intermediate film is thinner than the thickness of the inner film in this manner, the laminated film is lengthened to be stocked as an intermediate product in a rolled state more easily than the inner film. Therefore, the stocked intermediate product can be laminated to a newly produced inner film, so that a multilayer film for containers is produced through fewer steps.

[0055] (Container) The container of the present invention is a container formed using the multilayer film for containers of the present invention. The container of the present invention can be used as a container that houses contents that cause a problem of deterioration due to oxidation, such as a container for food, a medical container and a container for various chemicals. In particular, the container of the present invention is suitable for use as a medical container. Examples of the medical container include a container that houses a drug solution, such as an injection bag, an IV bag or an infusion bag. Fig. 3 is a view illustrating an embodiment of a container C formed using the multilayer film for containers of the present invention, and illustrates an example of the infusion bag which is a medical container. The container C (infusion bag which is a medical container) illustrated in Fig. 3 is constituted by the tubular multilayer film TF for containers illustrated in Fig. 2 which is an embodiment of the multilayer film for containers of the present invention. The container C illustrated in Fig. 3 can be produced by, for example, the following method. A spout is provided at a first end that is one opening end of the tubular multilayer film TF for containers, and the first end of the tubular multilayer film for containers and the side end of the tubular multilayer film for containers are heat-sealed to form an infusion solution housing portion 61, a first end heat-sealed portion 63a, and a side end heat-sealed portion 63c. Next, an infusion solution is charged into the infusion solution housing unit 61 from a second end that is the other opening end of the tubular multilayer film for containers with the first end heat-sealed portion 63a placed on the bottom, and thereafter the second end is heat-sealed to form a second end heat-sealed portion. A hanging hole 64 is formed by punching in the second end heat-sealed portion 63b, and unsealed portions 65a and 65b are formed on both sides thereof. The first end heat-sealed portion 63a is provided with a spout 62, and a rubber plug (not illustrated) into which an injection needle is inserted is attached to a distal end of the spout 62. The spout 62 may be a tube having a diameter slightly larger than the diameter of a spike. Alternatively, an unsealed portion may be provided in a part of the side end heat-sealed portion 63c, an infusion solution may be charged from the unsealed portion, and thereafter the unsealed portion may be sealed to complete the side end heat-sealed portion 63c.

[0056] (Method for producing container) The method for producing the container of the present invention is not particularly limited. For example, when the multilayer film F for containers illustrated in Fig. 1 is used, two multilayer films F for containers can be stacked such that the skin layers (sealant layers) of the inner films are in contact with each other, and thereafter heat-sealed, thereby to produce a container. For example, when the multilayer film TF for containers illustrated in Fig. 2 is used, a container can be produced by heat-sealing the inner surfaces of the flat tubular inner films. When the multilayer film TF for containers illustrated in Fig. 2 is used, the inner surface of the container is not exposed to outside air, so that it is possible to produce a container which is not contaminated with bacteria and foreign matters and is excellent in hygiene properties. Such a container is useful for a bag-shaped infusion bag or the like. An example of the heat-sealing of the multilayer film for containers is a method for heat-sealing the multilayer film for containers into a bag form by heat-pressing the multilayer film for containers from the outer film side. By this method, a bag-shaped container can be obtained. In addition, a medical container such as an infusion bag can be obtained by, for example, cutting off a part of a heat seal of the multilayer film for containers after heat sealing in which the shape of the heat seal is obtained by removing a portion to be filled with contents, and then welding a tube or the like to serve as an injection port 62a.

[0057] (Drug solution-containing medical container) The drug solution-containing medical container of the present invention is a container constituted by the multilayer film for containers of the present invention in which a drug solution is housed. Examples of the drug solution housed in the drug solution-containing medical container of the present invention include a drug which is easily oxidized and / or a drug which is easily adsorbed to polyolefin. Examples of such a drug include an anticancer agent, an antidepressant, a brain protectant (for example, edaravone(3-methyl-1-phenyl-2-pyrazolin-5-one)), vitamin A, and vitamin D. The drug solution-containing medical container of the present invention can secure a generally required expiration date of about three years even for a drug that is sensitive to oxygen and has a concern of lowering in the titer due to adsorption.

[0058] Hereinafter, the present invention will be described in detail by Examples, but the present invention is not limited by the following description.

[0059] (Materials used) VM-PET; A transparent silica-deposited high gas barrier film having a thickness of 12 μm, manufactured by Mitsubishi Chemical Corporation, trade name ”TECHBARRIER LS”, oxygen transmissivity: 1 mL / (m2・day・MPa), water vapor transmissivity: 0.1 g / (m2・day) LL; Linear low density polyethylene, manufactured by Japan Polyethylene Corporation, trade name ”Harmolex”, MFR: 0.9 g / 10 min, density: 0.91 g / cm3 HD1; High density polyethylene, manufactured by Japan Polyethylene Corporation, trade name ”NOVATEC HD HM160”, MFR: 5 g / 10 min, density: 0.950 g / cm3 HD2; High density polyethylene, manufactured by Japan Polyethylene Corporation, trade name ”NOVATEC HD HM4503”, MFR: 1.9 g / 10 min, density: 0.960 g / cm3 Tie1; Olefin (polypropylene)-based thermoplastic elastomer, manufactured by Mitsubishi Chemical Corporation, trade name ”ZELAS MC721AP”, MFR: 3.2 g / 10 min, density: 0.89 g / cm3 Tie2; Polyethylene-based adhesive resin, manufactured by Mitsubishi Chemical Corporation, trade name ”MODIC”, MFR: 1.5 g / 10 min, density: 0.91 g / cm3 O2TRP; Ethylene-vinyl alcohol copolymer-based resin having oxygen absorbing capability, manufactured by Kuraray Co., Ltd, trade name ”EVAL AP931B”, MFR: 3.5 g / 10 min, density: 1.17 g / cm3 EVOH; Ethylene-vinyl alcohol copolymer, manufactured by Kuraray Co., Ltd, trade name ”EVAL L171B”, MFR: 4.0 g / 10 min, density: 1.21 g / cm3 COP; Kneaded mixture of cyclic polyolefins COP1 and COP2 below at 5:5, only one observed glass transition temperature of mixture: 119°C COP1; Cyclic polyolefin as a hydrogenated product of a ring-opening polymer of a cyclic olefin monomer, manufactured by Zeon Corporation, trade name ”ZEONEX 690R”, MFR (280°C): 17 g / 10 min, density: 1.01 g / cm3, glass transition temperature:136°C COP2; Cyclic polyolefin as a hydrogenated product of a ring-opening polymer of a cyclic olefin monomer, manufactured by Zeon Corporation, trade name ”ZEONOR 1020R”, MFR (280°C): 20 g / 10 min, density: 1.01 g / cm3, glass transition temperature: 102°C Polyurethane-based adhesive; Manufactured by Mitsubishi Chemical Corporation, ester-based polyol, trade name ”TAKELAC A-319” and aliphatic isocyanate, trade name ”TAKENATE S-50”

[0060] An intermediate film and an inner film were produced, and a film including these films and an outer film were bonded by dry lamination to produce a multilayer film for containers, and an infusion bag was produced with the produced multilayer film for containers and evaluated. Details are described below.

[0061] <Production of intermediate film> An intermediate film which is a coextruded film including five layers of three types was produced using an air-cooled inflation film forming machine. The intermediate film is a tubular film having a total thickness of 70 μm, in which a polyolefin layer that is a skin layer having a thickness of 20 μm and a mass ratio of LL / HD1 = 60 / 40 is bonded to both surfaces of a core layer having a thickness of 10 μm and containing O2TRP that is an ethylene-vinyl alcohol copolymer-based resin having oxygen absorbing capability by an adhesive resin having a thickness of 10 μm and containing Tie1. That is, the intermediate film is a tubular film having a symmetrical laminated structure in which the configuration of skin layer / adhesive layer / core layer / adhesive layer / skin layer is (LL / HD1 = 60 / 40) / Tie1 / O2TRP / Tie1 / (LL / HD1 = 60 / 40), and the thickness is 20 μm / 10 μm / 10 μm / 10 μm / 20 μm. The obtained tubular film was cut at two locations, and two films obtained by cutting open the tubular film were wound around individual winding cores to obtain two roll films having a width of 860 mm.

[0062] <Production of inner film> An inner film which is a coextruded film including five layers of three types was produced using a water-cooled inflation film forming machine. The inner film is a tubular film having a total thickness of 150 μm, in which a skin layer having a thickness of 20 μm and containing HD2 is laminated on both surfaces of a core layer having a thickness of 20 μm and containing COP via an intermediate layer having a thickness of 45 μm and containing a mixed resin having a mass ratio of LL / HD2 = 80 / 20 in which LLDPE is the main component. That is, the inner film is a tubular film having a symmetrical laminated structure in which the configuration of skin layer / intermediate layer / core layer / intermediate layer / skin layer is HD2 / (LL / HD2 = 80 / 20) / COP / (LL / HD2 = 80 / 20) / HD2, and the thickness is 20 μm / 45 μm / 20 μm / 45 μm / 20 μm. The tubular film was deformed and flattened, and wound around a winding core to obtain a roll film in which a flat tubular inner film having a width of 310 mm was wound. Both ends in the longitudinal direction of the tubular film were heat-sealed to prevent the inner surface of the tube from coming into contact with outside air.

[0063] <Production of multilayer film for containers> A surface of a VM-PET having a width of 860 mm on a vapor deposited layer side, on which a polyurethane-based adhesive was applied and dried, was bonded to one surface of an intermediate film subjected to corona treatment by dry lamination to produce a laminate film. The laminate film was slit to a width of 260 mm. Next, the other surface of the intermediate film of the laminate film, which was subjected to corona treatment and thereafter applied with a polyurethane-based adhesive and dried, was bonded to both surfaces of a flat tubular inner film by dry lamination. As a result, a roll film of a flat tubular multilayer film for containers having, as a core layer, a flat tubular inner film in which films were bonded in a structure of outer film / intermediate film / flat tubular inner film / intermediate film / outer film was obtained. Similarly, in this multilayer film for containers, both ends in the longitudinal direction of the flat tubular inner film are heat-sealed, and the inner surface of the tube is not in contact with outside air. In the dry lamination step, the intermediate film immediately after being unwound from the roll film was not curled, no problem occurred in the subsequent dry lamination step, and the processing suitability was good.

[0064] <Production of infusion bag> The obtained multilayer films for containers were set in a bag making machine, and the inner surfaces on the inner film side of three edges excluding one short edge of the substantially rectangular shape were heat-sealed at 215°C. Thereafter, the product was cut out into an infusion bag shape with a Thomson blade so as to have a substantially rectangular container shape with an inner size of about 85 mm × 180 mm. One tube having an inner diameter of 6 mm and an outer diameter of 8 mm was inserted into one side of the cut-out container which was not heat-sealed, and was welded by heat sealing. At this time, the inner surfaces of the multilayer films for containers around the tube welded portion were also heat-sealed at the same time, and the infusion bag was completely sealed except for the opening of the tube. Thus, an infusion bag having a rated capacity of 100 mL was obtained. The material of the tube used was obtained by blending a thermoplastic elastomer and a polypropylene resin.

[0065] <Characteristics evaluation> The following characteristics were evaluated for the obtained multilayer films for containers or infusion bags. The results are illustrated in Table 1.

[0066] (Degree of curling) A 10 cm square film piece was cut out from the multilayer film for containers, and stored in an environment at a temperature of 40°C and a humidity of 90% for 24 hours. The film piece was spread on a flat surface, and the height at which both end surfaces were curled was measured and evaluated according to the following criteria. As the height is lower, curling is suppressed, and the film is substantially free from curling and easy to handle. A: Height of less than 1 cm B: Height of equal to or more than 1 cm and less than 3 cm C: Height of 3 cm or more

[0067] (Shrinkage rate) Straight marks orthogonal to the machine direction of the multilayer film for containers before autoclave treatment were provided at intervals of 100 mm in the machine direction, and the ratio at which the interval of 100 mm was shortened after the autoclave treatment at 121°C for 30 minutes was defined as the shrinkage rate.

[0068] (Interlayer adhesive strength) A strip piece having a length of 50 mm and a width of 15 mm was cut out from the infusion bag in the longitudinal direction of the multilayer film for containers, and the layers at the end of the strip piece were peeled off. Thereafter, the interlayer adhesive strength when each layer peeled off was pulled at a tensile rate of 300 mm / min was measured in accordance with JIS Z0238 before autoclave treatment and after the autoclave treatment at 121°C for 30 minutes. The measured interlayer adhesive strength is the interlayer adhesive strength between the adhesive layer and the oxygen absorbing layer in the coextruded intermediate film. This measured interlayer adhesive strength is the adhesive strength of an interlayer having the lowest adhesive strength among a plurality of interlayers in the multilayer film for containers.. Measurement of the interlayer adhesive strength was attempted at two locations between the outer film and the intermediate film and between the intermediate film and the inner film which were produced by dry lamination, but the adhesion was so strong that the layers could not be peeled off.

[0069] (Transparency) On the basis of “The Japanese Pharmacopoeia 17th edition”,“7.02 Test Methods for Plastic Containers”, ”2. Standard of plastic containers for aqueous injections”, ”2.1. Polyethylene or polypropylene containers for aqueous injections”, the value of light transmittance was measured before autoclave treatment and after the autoclave treatment at 121°C for 30 minutes.

[0070] (Oxygen absorbing capability) In a transparent oxygen barrier bag (hereinafter, referred to as an ”inner bag”) made of a laminate film of a vapor deposited PET film having a thickness of 12 μm and a CPP film having a thickness of 50 μm, about 200 mL of precisely weighed water, a multilayer film for containers having an area of 25cm2of a 5 cm square, and a glass-based sensor chip for enabling measurement with a non-contact oximeter (Fibox 3 trace manufactured by PreSens) capable of measuring the dissolved oxygen concentration from the outside of the inner bag were enclosed in such a manner as to eliminate the air as much as possible. The initial dissolved oxygen concentration in the inner bag before autoclave treatment was measured using the non-contact oximeter. The inner bag was vacuum-packed by an aluminum laminated bag (hereinafter, referred to as an ”outer bag”), and thereafter subjected to autoclave treatment at 121°C for 30 minutes. Then, the inner bag was taken out from the outer bag at 23°C, and the dissolved oxygen concentration was measured. Again, the inner bag was vacuum-packed in the outer bag and left to stand in a thermostatic bath at 50°C. The operation of taking out the inner bag from the outer bag and measuring the dissolved oxygen concentration at 23°C was repeated every 24 hours to several days. The value when there was no change in the dissolved oxygen concentration toward the decrease by this operation was defined as the final dissolved oxygen concentration, and the measurement was terminated. The oxygen absorbing capability per unit area was determined by the following equation: oxygen absorbing capability per unit area (mg / cm2) = ((initial dissolved oxygen concentration (mg / L) - final dissolved oxygen concentration (mg / L)) x amount of water (L)) / 25 (cm2).

[0071] (TOC (total organic carbon)) Purified water for TOC measurement (manufactured by FUJIFILM Wako Pure Chemical Corporation) is charged into an infusion bag in such a volume that the ratio to the inner surface area of the infusion bag is 6 mL / cm2, and a tube is heat-sealed. Next, the infusion bag was subjected to autoclave treatment at 121°C for 1 hour, the purified water after cooling was collected, and the TOC (total organic carbon) was measured by a TOC meter (total organic carbon meter TOC-LCSH manufactured by Shimadzu Corporation).

[0072] (Drug residual rate) In 850 mL of water for injection, 1.5 g of edaravone(3-methyl-1-phenyl-2-pyrazoline-5-one), 1.0 g of sodium bisulfite, 0.5 g of L-cysteine hydrochloride monohydrate, 6.75 g of sodium chloride, and 2.1 g of phosphoric acid were dissolved, and the pH was adjusted to 3.7 with an appropriate amount of sodium hydroxide. Then, the total amount was adjusted to 1 L with water for injection. This was added with 5 L of physiological saline to obtain a 0.25 mg / mL aqueous solution of edaravone as a model drug solution. The concentration of edaravone in the model drug solution was measured under the following conditions using HPLC. Detector: Ultraviolet absorptiometer (measurement wavelength: 240 nm) Column: Shodex C18M 4D Column temperature: 50°C Mobile phase: A solution prepared by adjusting the pH of a mixed solution of a 10 mM acetic acid aqueous solution and methanol (3:1) to 5.5 with aqueous ammonia Flow rate: Adjusted such that the retention time of edaravone is about 8 minutes In an infusion bag having a rated capacity of 100 mL, 100 mL of the model drug solution was poured, and a tube was heat-sealed. The infusion bag was directly subjected to autoclave treatment at 121°C for 30 minutes, and thereafter stored at 60°C. After 1 month, the edaravone concentration in the model drug solution of the infusion bag was measured, and the residual rate (%) was examined by comparing to the initial concentration.

[0073] (Heat resistance) The infusion bag was directly subjected to autoclave treatment at 121°C for 30 minutes. Thereafter, the appearance was visually evaluated according to the following criteria. A: The film has no wrinkles. B: The film is slightly wrinkled, but there is no practical problem. C: The film has wrinkles, and / or delamination in which layers are partly peeled off occurs, so that there is a portion appearing white. Evaluation A is excellent in heat resistance, but Evaluation C is poor in heat resistance.

[0074] <Evaluation of suitability for medical container> In order to evaluate the suitability for a medical container (infusion bag), a test based on “The Japanese Pharmacopoeia 17th edition”,“7.02 Test Methods for Plastic Containers”, ”2. Standard of plastic containers for aqueous injections”, ”2.1. Polyethylene or polypropylene containers for aqueous injections” was performed to evaluate the suitability for a medical container. The results are illustrated in Table 2.

[0075] In the same manner as in Example 1, a multilayer film for containers was produced, and an infusion bag was obtained, except that Tie2 was used instead of Tie1 of the adhesive resin of the adhesive layer of the intermediate film. The results of the characteristics evaluation are illustrated in Table 1, and the results of the evaluation of suitability for a medical container are illustrated in Table 3.

[0076] In the same manner as in Example 1, a multilayer film for containers was produced, and an infusion bag was obtained, except that in Example 1, the skin layer of the intermediate film was changed to a mixed resin having a mass ratio of LL / HD1 = 80 / 20, and that the intermediate layer of the inner film was changed to only LL. The results of the characteristics evaluation are illustrated in Table 1.

[0077] Using the multilayer film for containers and the infusion bag obtained in Example 3, characteristics evaluation was performed by changing the autoclave treatment temperature from 121°C to 110°C in the evaluations on the shrinkage rate, the interlayer adhesive strength, the transparency, the drug residual rate, and the heat resistance. The results of the characteristics evaluation are illustrated in Table 1.Comparative Example 1

[0078] The characteristics were evaluated in the same manner as in Example 1, except that EVOH was used instead of O2TRP which is the core layer in the intermediate film, and that transparency was not evaluated. The results of the characteristics evaluation are illustrated in Table 1.Comparative Example 2

[0079] The characteristics were evaluated in the same manner as in Example 1, except that a mixture having a mass ratio of LL / HD2 = 80 / 20 was used instead of COP which is the core layer in the inner film, and that transparency was not evaluated. The results of the characteristics evaluation are illustrated in Table 1.Comparative Example 3

[0080] Using an air-cooled inflation film forming machine for a multilayer film including nine layers of nine types, a flat tubular film having a folded width of 1000 mm was produced in which the configuration of seven layers of five types that is surface layer / adhesive layer / oxygen absorbing layer / adhesive layer / COP / mixed resin layer / surface layer in order from the outside of the film forming bubble was (LL / HD1 / LD = 60 / 20 / 20) / Tie1 / O2TRP / Tie1 / COP / (LL / HD1 = 80 / 20) / (LL / HD1 / LD = 60 / 20 / 20). This film is a coextruded film having an asymmetrical layer configuration in which the thickness of each layer is 20 μm / 15 μm / 20 μm / 15 μm / 20 μm / 40 μm / 30 μm in order from the outside with a total thickness of 160 μm. A surface having a vapor deposited layer of VM-PET having a width of 910 mm was bonded to both surfaces of the flat tubular film by a polyurethane-based adhesive. As a result, a flat tubular multilayer film for containers having the structure of outer film / flat tubular film / outer film and including a flat tubular film as the core layer was obtained. The flat tubular multilayer film for containers was slit to a width of 260 mm to obtain a roll film of two sheets including the front-side film and the back-side film. When the roll film of two sheets of multilayer films for containers was set in a bag forming machine of an infusion bag, and the two sheets were unwound in a stacked state, the light blocking on the inner surface was peeled off each time the roll film was unwound due to a difference in circumferential length between the front side and the back side, the film on the front side was slack, and continuous bag formation was not possible. Therefore, an infusion bag having the same shape as that of Example 1 was produced by producing the bag while correcting the slack little by little. The characteristics were evaluated in the same manner as in Example 1, except that transparency was not evaluated for the obtained multilayer film for containers or infusion bag. The results of the characteristics evaluation are illustrated in Table 1.

[0081]

[0082]

[0083]

[0084] In Example 2 in which a polyethylene-based adhesive resin was used for the adhesive layer of the intermediate film, the interlayer adhesive strength between the oxygen absorbing layer as the core layer and the adhesive layer was higher than that in Example 1 in which an olefin (polypropylene)-based thermoplastic elastomer was used for the adhesive layer. In particular, the interlayer adhesive strength after autoclave treatment was twice or more. In Examples 3 and 4 in which the amount of linear low density polyethylene (LL) used was increased in the skin layer of the intermediate film and the intermediate layer of the inner film, transparency was excellent both before and after autoclave treatment. In Example 3 in which the autoclave treatment temperature was 121°C, the evaluation of heat resistance was C, the appearance of the infusion bag after autoclave treatment was deteriorated, and the drug residual rate was slightly lowered. On the other hand, in Example 4 in which the film configuration was the same as that in Example 3, and the autoclave treatment temperature was 110°C, the evaluation of heat resistance was A, and the shrinkage rate and the drug residual rate were both excellent. When a certain content such as a drug solution is sterilized with high-pressure steam at 121°C, the components in the content are intensely decomposed. Therefore, sterilization with high-pressure steam may be performed at 110°C. The multilayer film for containers and the infusion bag of Example 4 can be said to be useful in the case of performing high-pressure steam sterilization at 110°C. Examples 1, 3, and 4 in which an olefin (polypropylene)-based thermoplastic elastomer was used for the adhesive layer of the intermediate film were superior in transparency to Example 2 in which a polyethylene-based adhesive resin was used for the adhesive layer. In Comparative Example 1 in which the oxygen absorbing layer of the intermediate film of Example 1 was an EVOH having no oxygen absorbing capability, the drug residual rate was low. In Comparative Example 2 in which a mixture of LL and HD2 was used instead of COP for the core layer of the inner film of Example 1, the drug residual rate was extremely low. Comparative Example 3 has the oxygen absorbing layer and the layer including COP, but was poor in bag forming suitability, had a large degree of curling, and was difficult to handle. In addition, in the evaluation of heat resistance, delamination in which layers are partly peeled off occurred.List of Reference Signs

[0085] F: Multilayer film for containers TF: Multilayer film for containers (inner film is flat tubular) 1: Outer film 2: Intermediate film 21: Intermediate film skin layer 22: Intermediate film adhesive layer 23: Intermediate film core layer 3: Inner film 3a: Inner film (flat tubular inner film) 31: Inner film skin layer 32: Inner film intermediate layer 33: Inner film core layer 4: Adhesive layer 5: Adhesive layer C: Container (medical container (infusion bag)) 61: Infusion solution housing portion 62: Spout 62a: Injection port 63a: First end heat-sealed portion 63b: Second end heat-sealed portion 63c: Side end heat-sealed portion 64: Hanging hole 65a, 65b: Unsealed portion

Claims

1. A multilayer film for containers comprising: an outer film which is a transparent oxygen barrier film; an intermediate film which is a coextruded film having an oxygen absorbing layer; and an inner film which is a coextruded film having a cyclic polyolefin layer containing cyclic polyolefin, wherein the intermediate film has a symmetrical laminated structure having a skin layer with the oxygen absorbing layer as a core layer, and the inner film has a symmetrical laminated structure having a skin layer with the cyclic polyolefin layer as a core layer.

2. The multilayer film for containers according to claim 1, wherein the intermediate film has a skin layer containing polyolefin on both surfaces of the core layer via an adhesive layer containing a polyethylene-based adhesive resin.

3. The multilayer film for containers according to claim 2, wherein the skin layer containing polyolefin contains 50 mass% or more of linear low density polyethylene and equal to or more than 30 mass% and less than 50 mass% of high density polyethylene.

4. The multilayer film for containers according to claim 1 or 2, wherein the inner film is flat tubular, and has the intermediate film and the outer film on both surfaces of the inner film.

5. A container comprising the multilayer film for containers according to claim 1 or 2.

6. A method for producing a container, comprising sealing the inner film of the multilayer film for containers according to claim 1 or 2.

7. A drug solution-containing medical container, wherein a drug solution is housed in the container according to claim 5.

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